20-62160042-T-C

Variant names:

• chr20-62160042-T-C
• rs6121926
• NM_198935.3:c.231+81T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198935.3(SS18L1):​c.231+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,392,432 control chromosomes in the GnomAD database, including 27,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (10484 hom., cov: 27)
  • Exomes 𝑓: 0.14 (17471 hom.)
• Consequence: SS18L1 NM_198935.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.322
• Publications: 8 publications found

Genes affected

SS18L1 (HGNC:15592): (SS18L1 subunit of BAF chromatin remodeling complex) This gene encodes a calcium-responsive transactivator which is an essential subunit of a neuron-specific chromatin-remodeling complex. The structure of this gene is similar to that of the SS18 gene. Mutations in this gene are involved in amyotrophic lateral sclerosis (ALS). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

SS18L1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-62160042-T-C is Benign according to our data. Variant chr20-62160042-T-C is described in CliVar as Benign. Clinvar id is 1274683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62160042-T-C is described in CliVar as Benign. Clinvar id is 1274683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62160042-T-C is described in CliVar as Benign. Clinvar id is 1274683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62160042-T-C is described in CliVar as Benign. Clinvar id is 1274683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SS18L1	NM_198935.3	c.231+81T>C		intron_variant	Intron 3 of 10	ENST00000331758.8	NP_945173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SS18L1	ENST00000331758.8	c.231+81T>C		intron_variant	Intron 3 of 10	1	NM_198935.3	ENSP00000333012.3
SS18L1	ENST00000450482.5	c.240+81T>C		intron_variant	Intron 4 of 4	5		ENSP00000398634.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 41860 AN: 150638 Hom.: 10446 Cov.: 27

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.136 AC: 169299 AN: 1241676 Hom.: 17471 AF XY: 0.138 AC XY: 85315 AN XY: 617706

African (AFR) AF: 0.700 AC: 19857 AN: 28368

American (AMR) AF: 0.121 AC: 4037 AN: 33490

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 4398 AN: 22790

East Asian (EAS) AF: 0.136 AC: 4785 AN: 35166

South Asian (SAS) AF: 0.225 AC: 16752 AN: 74368

European-Finnish (FIN) AF: 0.0896 AC: 3356 AN: 37452

Middle Eastern (MID) AF: 0.171 AC: 913 AN: 5350

European-Non Finnish (NFE) AF: 0.112 AC: 106508 AN: 951838

Other (OTH) AF: 0.164 AC: 8693 AN: 52854

GnomAD4 genome AF: 0.278 AC: 41956 AN: 150756 Hom.: 10484 Cov.: 27 AF XY: 0.275 AC XY: 20215 AN XY: 73588

African (AFR) AF: 0.676 AC: 27531 AN: 40722

American (AMR) AF: 0.161 AC: 2438 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3464

East Asian (EAS) AF: 0.174 AC: 892 AN: 5114

South Asian (SAS) AF: 0.244 AC: 1157 AN: 4748

European-Finnish (FIN) AF: 0.0937 AC: 982 AN: 10484

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7684 AN: 67788

Other (OTH) AF: 0.230 AC: 481 AN: 2090

Alfa AF: 0.165 Hom.: 14030

Bravo AF: 0.300

Asia WGS AF: 0.242 AC: 843 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.68
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6121926; hg19: chr20-60735098; COSMIC: COSV59210118; COSMIC: COSV59210118;